Non-aqueous silicone elastomer gels as a vaginal microbicide delivery system for the HIV-1 entry inhibitor maraviroc

Aqueous semi-solid polymeric gels, such as those based on hydroxyethylcellulose (HEC) and polyacrylic acid (e.g. Carbopol®), have a long history of use in vaginal drug delivery. However, despite their ubiquity, they often provide sub-optimal clinical performance, due to poor mucosal retention and limited solubility for poorly water-soluble actives. These issues are particularly pertinent for vaginal HIV microbicides, since many lead candidates are poorly water-soluble and where a major goal is the development of a coitally independent, once daily gel product. In this study, we report the use of a non-aqueous silicone elastomer gel for vaginal delivery of the HIV-1 entry inhibitor maraviroc. In vitro rheological, syringeability and retention studies demonstrated enhanced performance for silicone gels compared with a conventional aqueous HEC gel, while testing of the gels in the slug model confirmed a lack of mucosal irritancy. Pharmacokinetic studies following single dose vaginal administration of a maraviroc silicone gel in rhesus macaques showed higher and sustained MVC levels in vaginal fluid, vaginal tissue and plasma compared with a HEC gel containing the same maraviroc loading. The results demonstrate that non-aqueous silicone gels have potential as a formulation platform for coitally independent vaginal HIV microbicides.

The good our field can hope to do, the harm it should avoid

This paper tries to achieve a balanced view of the ethical issues raised by emotion-oriented technology as it is, rather than as it might be imagined. A high proportion of applications seem ethically neutral. Uses in entertainment and allied areas do no great harm or good. Empowering professions may do either, but regulatory systems already exist. Ethically positive aspirations involve mitigating problems that already exist by supporting humans in emotion-related judgments, by replacing technology that treats people in dehumanized and/or demeaning ways, and by improving access for groups who struggle with existing interfaces. Emotion-oriented computing may also contribute to revaluing human faculties other than pure intellect. Many potential negatives apply to technology as a whole. Concerns specifically related to emotion involve creating a lie, by simulate emotions that the systems do not have, or promoting mechanistic conceptions of emotion. Intermediate issues arise where more general problems could be exacerbated-helping systems to sway human choices or encouraging humans to choose virtual worlds rather than reality. "SIIF" systems (semi-intelligent information filters) are particularly problematic. These use simplified rules to make judgments about people that are complex, and have potentially serious consequences. The picture is one of balances to recognize and negotiate, not uniform good or evil. © 2010-2012 IEEE.

ASR emotional speech: Clarifying the issues and enhancing performance

There are multiple reasons to expect that recognising the verbal content of emotional speech will be a difficult problem, and recognition rates reported in the literature are in fact low. Including information about prosody improves recognition rate for emotions simulated by actors, but its relevance to the freer patterns of spontaneous speech is unproven. This paper shows that recognition rate for spontaneous emotionally coloured speech can be improved by using a language model based on increased representation of emotional utterances. The models are derived by adapting an already existing corpus, the British National Corpus (BNC). An emotional lexicon is used to identify emotionally coloured words, and sentences containing these words are recombined with the BNC to form a corpus with a raised proportion of emotional material. Using a language model based on that technique improves recognition rate by about 20%. (c) 2005 Elsevier Ltd. All rights reserved.

PicSOr - An objective test of perceptual skill that predicts laparoscopic technical skill in three initial studies of laparoscopic performance

Background: Laparoscopic surgery requires surgeons to infer the shape of 3-D structures, such as the internal organs of patients, from 2-D displays on a video monitor. Recent evidence indicates that the issue is not resolved by the use of contemporary 3-D camera systems. It is therefore crucial to find ways of measuring differences in aptitude for recovering 3-D structure from 2-D images, and assessing its impact on performance. Our aim was to test empirically for a relationship between laparoscopic ability and the perceptual skill of recovering information about 3-D structures from 2-D monitor displays.

Charged experience's of natural environments

Natural environments often generate experiences that combine great emotional and moral power- "charged" experiences. Their characteristics are explored through writings that capture them convincingly. They appear to have a perceptual character. Perception of the scene is invested with a sense of something beyond it, and much bigger. It may be God, or immensity in time or space, or the essence of a nation. This encounter is often connected with moral authority. A recurring theme is the sense that environment and the things in it-including the observer-are a self-similar pattern. People are not passive recipients of these experiences. They seek them out. Evoking, the environment in words can often evoke the charged experience too-at least in part. The material suggests tasks for psychologists-most simply, finding systematic ways to describe these experiences. That may help other environmental disciplines, which face difficulty characterising the dimension of response. Theoretically, the material raises questions about the representations generated by perceptual processes. The observation that powerful moral imperatives seem to be given in the act of perceiving is also suggestive for the psychology of morality. Culture certainly plays a part in charged responses, but landscapes have the power to be invested with an emotional and moral charge where other stimuli may not.